Evidence map›Paper›PMID 30503861›Full record

ArticleEBioMedicine2018

Protease activity sensors noninvasively classify bacterial infections and antibiotic responses.

Colin G Buss, Jaideep S Dudani, Reid T K Akana, Heather E Fleming, Sangeeta N Bhatia

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 28 citations in OpenAlex.

  1. Erasable serum markers.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Host protease activity classifies pneumonia etiology.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  7. Article
  8. Article
  9. Article
  10. Nanotechnology in pulmonary medicine.Current opinion in pharmacology · 2021
    Review
  11. Review
  12. Article
  13. Review
  14. QnAs with Sangeeta N. Bhatia.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Colin G BussKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Health Sciences and Technology Program, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jaideep S DudaniKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Reid T K AkanaDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Heather E FlemingKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Health Sciences and Technology Program, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sangeeta N BhatiaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Health Sciences and Technology Program, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Cambridge, MA 02139, USA. Electronic address: sbhatia@mit.edu.
Massachusetts Institute of Technology · USBroad Institute · US

Funding

Macrophage-targeting Nanoplatforms as Immunotherapy against Pulmonary InfectionsR01AI132413 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael J Sailor · 2017 to 2026
$6.0M
NIAID NIH HHS R01 AI132413
6 · The paper itself

Abstract

backgroundRespiratory tract infections represent a significant public health risk, and timely and accurate detection of bacterial infections facilitates rapid therapeutic intervention. Furthermore, monitoring the progression of infections after intervention enables 'course correction' in cases where initial treatments are ineffective, avoiding unnecessary drug dosing that can contribute to antibiotic resistance. However, current diagnostic and monitoring techniques rely on non-specific or slow readouts, such as radiographic imaging and sputum cultures, which fail to specifically identify bacterial infections and take several days to identify optimal antibiotic treatments.

methodsHere we describe a nanoparticle system that detects P. aeruginosa lung infections by sensing host and bacterial protease activity in vivo, and that delivers a urinary detection readout. One protease sensor is comprised of a peptide substrate for the P. aeruginosa protease LasA. A second sensor designed to detect elastases is responsive to recombinant neutrophil elastase and secreted proteases from bacterial strains.

findingsIn mice infected with P. aeruginosa, nanoparticle formulations of these protease sensors-termed activity-based nanosensors (ABNs)-detect infections and monitor bacterial clearance from the lungs over time. Additionally, ABNs differentiate between appropriate and ineffective antibiotic treatments acutely, within hours after the initiation of therapy.

interpretationThese findings demonstrate how activity measurements of disease-associated proteases can provide a noninvasive window into the dynamic process of bacterial infection and resolution, offering an opportunity for detecting, monitoring, and characterizing lung infections. FUND: National Cancer Institute, National Institute of Environmental Health Sciences, National Institutes of Health, National Science Foundation Graduate Research Fellowship Program, and Howard Hughes Medical Institute.

Indexed as

AnimalsAnti-Bacterial AgentsBacteriaBacterial InfectionsBiosensing TechniquesDisease Models, AnimalFemaleHost-Pathogen InteractionsHumansMiceNanoparticlesPeptide HydrolasesPseudomonas aeruginosaPseudomonas InfectionsROC CurveSubstrate SpecificityAnti-Bacterial AgentsPeptide HydrolasesBacterial pneumoniaDiagnosticNanoparticleProtease

Identifiers

PMID30503861
PMCPMC6306379
OpenAlexW2902549952

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.